The need for combating the growth of undesirable microorganisms, bacteria, insects, and the like is a continuing and increasing one. Many organic compounds have been suggested as a deterrent to such growth or as an effective destroyer of the undesired life.
As compared to a mere killing or destroying of microorganisms, etc., a quite different situation prevails when one is concerned with killing only one of two cohabiting classes of living things without harming the other. A common example of this is undesirable parasitic infestation on a desirable, living, warm-blooded, animal.
More specifically, various types of worm parasites are found in mammals of commercial importance to man. The most important are the parasites of livestock, especially of ruminants, such as sheep, goats, and cattle. However, other ruminants are similarly affected such as oxen, deer, water buffalo, etc. The more significant parasites are the nematodes (worms) of the alimentary tracts and the trematodes (flukes) which infect the liver. The alimentary tract nematodes are principally important insofar as they raduce the growth of the host animals and render less efficient the consumption of feed by the animals. The trematodes directly affect a vital organ and can cause severe illness and death in the host animal.
Obviously, a treating agent which not only kills parasites, but also kills the host animal is of no utility. Conversely, a treating agent that is harmless on the host animal but only slightly retards the growth of parasitic life is of little real value. What is needed is a treating agent that not only kills or expels the parasites, but which is harmless to the host; or for which the host has a large margin of tolerance, that is, an agent of which the host can take massive dosages with little or no harm. Moreover, although both types of mentioned infestations, the nematodes and the trematodes, occur commonly and naturally in the same types of livestock, presently known medications normally used for control on one of these infections is generally ineffective for the control of the other.
The matter of tolerance of a host animal for a therapeutic agent, such as an anthelmintic, cannot be overemphasized, especially when the animal must be administered to from a group or herd of animals in an unavoidably somewhat imprecise manner. In the treatment of large groups there is serious risk that some animals may be inadvertantly treated more than once, and thus subjected to double or triple dosage; that some animals will be overdosed because of errors in estimating their individual weights; that some animals will, by virtue of individual genetic variation, and variable state of health or ability, have less tolerance than the average animal for any medication, It is therefore clearly desirable that the typical animal be able to tolerate without serious harm, as large a multiple as possible of the minimum dosage regarded a likely to be effective as an anthelmintic.
The difference in activity between an effective amount of an anthelmintic on parasites and on a host animal can be quantitatively expressed as a Therapeutic Index. This index is defined as the maximum dose at which no toxic symptoms in the host animal are observed, divided by the minimum dose at which the anthelmintic is therapeutically effective. In general, an anthelmintic is considered to be therapeutically effective against a given parasite when it kills or expells from the host at least 80% and preferably close to 100% of the viable forms of that parasite.